Safety of Dabigatran Etexilate in Blood Clot Prevention i... | NCT02197416

NCT02197416

ID	Type	Description	Link
2014-000583-18	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
dabigatran etexilate	Experimental		Drug: dabigatran etexilate

Name	Type	Description	Arm Group Labels	Other Names
dabigatran etexilate	Drug	Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation	dabigatran etexilate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months	The event-free probability of first recurrence of VTE were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience recurrent VTE at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-VTE related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and 12 (Week 52) of on treatment period
Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months	The event-free probability of major or minor (including CRNM) bleeding event were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience major or minor (including CRNM) bleeding event at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-bleeding related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and month 12 (Week 52) of on treatment period
Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months	The event-free probability of mortality overall and related to thrombotic or thromboembolic events were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience mortality overall and related to thrombotic or thromboembolic events at the time of analysis, dropped out from the trial early, were lost to follow-up, were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and 12 (Week 52) of on treatment period

Secondary Outcomes

Measure	Description	Time Frame
Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months	The event-free probability of PTS were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience PTS at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-PTS related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Male or female subjects 0 to less than 18 years of age at the time of informed consent / assent
Previously documented objective diagnosis of VTE, followed by completed course of initial VTE treatment for at least 3 months (in case of VKA - intended INR between 2 and 3) or completed study treatment (i.e. reached Visit 8) in the 1160.106 trial. Patients, who during the treatment phase of 1160.106 trial were switched from dabigatran etexilate to SOC arm for any reason, are not eligible for this study.
Presence of an unresolved clinical risk factor requiring further anticoagulation for secondary VTE prevention (e.g. central venous line, underlying disease, thrombophilia, etc.)
Written informed consent form (ICF) provided by the patient's parent or legal guardian and assent provided by the patient (if applicable) at the time of ICF signature according to local regulations.
Further inclusion criteria apply

Exclusion criteria:

Conditions associated with an increased risk of bleeding
Renal dysfunction (eGFR < 50 mL/min/1.73m^2 using the Schwartz formula) or requirement for dialysis. eGFR retesting during the screening period is allowed (once).
Active infective endocarditis
Subjects with a heart valve prosthesis requiring anticoagulation.
Hepatic disease: Active liver disease, including known active hepatitis A, B or C or Persistent alanine aminotransferase (ALT) or aspartate transaminase (AST) or alkaline phosphatase (AP) > 3 × upper limit of normal (ULN) within 3 months of screening
Pregnant or breast feeding females. Females who have reached menarche and are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and / or do not agree to adhere to pregnancy testing required by this protocol
Patients in age group 0 to < 2 years with gestational age at birth < 37 weeks or with body weight lower than the 3rd percentile
Anemia (hemoglobin < 80g/L) or thrombocytopenia (platelet count < 80 x 109/L) at screening. Transfusions during the screening period are allowed, provided that a satisfactory hemoglobin or platelet level is attained prior to visit 2
Patients who have taken restricted medication prior to first dose of study medication
Patients who have received an investigational drug in the past 30 days prior to screening, except patients who have completed the treatment period (up to Visit 8) in 1160.106 trial
Patients who are allergic/sensitive to any component of the study medication including solvent
Patients or parents/legal guardians considered unreliable to participate in the trial per investigator judgment or any condition which would present a safety hazard to the patient based on investigator judgment
Further exclusion criteria apply

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of California Davis		Sacramento	California	95817	United States
University of Miami

PubMed Identifier	Type	Citation	Retractions
38348778	Derived	Albisetti M, Tartakovsky I, Halton J, Bomgaars L, Chalmers E, Mitchell LG, Luciani M, Nurmeev I, Gorbatikov K, Miede C, Brueckmann M, Brandao LR; Study Investigators. Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease. J Am Heart Assoc. 2024 Feb 20;13(4):e028957. doi: 10.1161/JAHA.122.028957. Epub 2024 Feb 13.
36150047

Label	URL
Related Info	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 7, 2019	May 5, 2020

Arm/Group Information

ID	Title	Description
BG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
BG001	Dabigatran Etexilate (2 to <12 Years)	Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and <12 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 2 to < 12 years.
BG002	Dabigatran Etexilate (12 to <18 Years)	Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 12 to <18 years.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months

The event-free probability of first recurrence of VTE were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months.

Patients who did not experience recurrent VTE at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-VTE related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

The treated set (TS) included all patients who were dispensed trial medication and had taken at least 1 dose of investigational treatment, which was used to assess safety endpoints, demographics and baseline characteristics.

Posted

Number

95% Confidence Interval

Probability

At month 6 (Week 26) and 12 (Week 52) of on treatment period

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)	Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and <12 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 2 to < 12 years.
OG002	Dabigatran Etexilate (12 to <18 Years)	Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 12 to <18 years.

Units	Counts
Participants	OG0009 OG00143 OG002161

Title

Denominators

Categories

6 months

Title	Measurements
	OG0001.000(1.000 to 1.000) OG0011.000(1.000 to 1.000) OG0020.979(0.937 to 0.993)

12 months

Primary

Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months

The event-free probability of major or minor (including CRNM) bleeding event were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months.

Patients who did not experience major or minor (including CRNM) bleeding event at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-bleeding related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

Posted

Number

95% Confidence Interval

Probability

At month 6 (Week 26) and month 12 (Week 52) of on treatment period

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.

Primary

Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months

The event-free probability of mortality overall and related to thrombotic or thromboembolic events were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months.

Patients who did not experience mortality overall and related to thrombotic or thromboembolic events at the time of analysis, dropped out from the trial early, were lost to follow-up, were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

Posted

Number

95% Confidence Interval

Probability

At month 6 (Week 26) and 12 (Week 52) of on treatment period

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.

Secondary

Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months

The event-free probability of PTS were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience PTS at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-PTS related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

Posted

Number

95% Confidence Interval

Probability

At month 6 (Week 26) and 12 (Week 52) of on treatment period

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.

Secondary

Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period

Percentage of participants with dabigatran etexilate dose adjustments during on treatment period. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

Posted

Number

Percentage of participants

From first DE administration to 3 days of residual effect period after last DE administration, up to 52 weeks+ 3 days

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)

Secondary

Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)

The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with non-missing endpoint values were included in this analysis.

Posted

Mean

Standard Deviation

Second (s)

At Visit 3 (day 4 after first dose of trial medication)

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)	Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and <12 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 2 to < 12 years.

Secondary

Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)

The PD set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.

Posted

Mean

Standard Deviation

Second (s)

Pharmacodynamics (PD) samples were collected from first dose of trial medication at day 1 and day 4, 22, 43, 85, 127, 183, 239 and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)

Secondary

Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)

The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.

Posted

Mean

Standard Deviation

Second (s)

At Visit 3 (day 4 after first dose of trial medication)

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)	Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and <12 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 2 to < 12 years.

Secondary

Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)

The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.

Posted

Mean

Standard Deviation

Second (s)

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)

Secondary

Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)

The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.

Posted

Mean

Standard Deviation

Second (s)

At Visit 3 (day 4 after first dose of trial medication)

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)	Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and <12 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 2 to < 12 years.

Secondary

Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)

The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.

Posted

Mean

Standard Deviation

Second (s)

dTT values were collected at day 4, 22, 43, 85, 127, 183, 239, and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.

ID	Title	Description
OG000	Dabigatran Etexilate (0 to < 2 Years)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 0 to <2 years.
OG001	Dabigatran Etexilate (2 to <12 Years)	Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and <12 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg. This arm includes participants aged between 2 to < 12 years.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dabigatran Etexilate (Treated Set)	Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months. Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years. Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years. Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and <250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg.	0	213	30	213	113	213

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial flutter	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Cardiac failure	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Myocarditis	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Pericardial effusion	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Ventricular pre-excitation	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Congenital anomaly	Congenital, familial and genetic disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Gastritis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Chest pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Oedema peripheral	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Hepatic vein stenosis	Hepatobiliary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Catheter site infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Cellulitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Encephalitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Gastroenteritis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Pneumonia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected213 at risk
Pulpitis dental	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Tonsillitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected213 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Metal poisoning	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Alanine aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Blood bilirubin increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Hepatic enzyme increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Acute lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Ewing's sarcoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Migraine	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Post-traumatic stress disorder	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Lupus nephritis	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Menstrual disorder	Reproductive system and breast disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Pelvic adhesions	Reproductive system and breast disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Bleeding varicose vein	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected213 at risk
Haematoma	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Lupus vasculitis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Phlebitis superficial	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk
Thrombosis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected213 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00013 affected213 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00015 affected213 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00015 affected213 at risk
Nausea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00017 affected213 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00015 affected213 at risk
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG00015 affected213 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG00034 affected213 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG00014 affected213 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG00011 affected213 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG00013 affected213 at risk
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG00034 affected213 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG00014 affected213 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG00014 affected213 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG00011 affected213 at risk

ID	Term
D013923	Thromboembolism
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring